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Genetic diversity of the Mycobacterium tuberculosis Beijing family in Brazil and Mozambique and relation with infectivity and induction of necrosis in THP-1 cells - 20/06/15

Doi : 10.1016/j.tube.2015.02.025 
Lia Lima Gomes a, Sidra Ezidrio Gonçalves Vasconcellos a, Harrison Magdinier Gomes a, Atina Ribeiro Elias a, Adalgiza da Silva Rocha a, Simone C.M. Ribeiro b, Alessandra Costa Panunto c, Lucilaine Ferrazoli d, Maria Alice da Silva Telles d, Araujo Marelo Emanuel Ivens de a, Afranio Lineu Kritski e, Igor Mokrousov f, Olga A. Manicheva g, Elena Lasunskaia b, Philip Noel Suffys a,
a Laboratory of Molecular Biology Applied to Mycobacteria, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil 
b Laboratory of Biology of Recognition, Universidade Estadual do Norte Fluminense, Rio de Janeiro, Brazil 
c Laboratory of Bacterial Pathogenesis and Molecular Biology, Unicamp, São Paulo, Brazil 
d Instituto Adolfo Lutz, São Paulo, Brazil 
e Laboratorio de Micobacteriologia Molecular do Centro de Pesquisas em Doenças Infecciosas e Parasitarias, University Hospital Clementino Fraga Filho, UFRJ, Rio de Janeiro, Brazil 
f Laboratory of Molecular Microbiology, St. Petersburg Pasteur Institute, St. Petersburg, Russia 
g Laboratory of Microbiology, Research Institute of Phthisiopulmonology, St. Petersburg, Russia 

Corresponding author. Tel.: +55 21 25621564; fax: +55 22 25621533.

Summary

Introduction

The success of the Mycobacterium tuberculosis Beijing (MtbB) lineage in different geographical regions has been attributed to high transmission, increased virulence, drug resistance and rapid adaptation to the host. In some countries of secondary MtbB dispersion like South Africa and Peru, rising prevalence of the Beijing strains is registered. However, in neighboring countries to affected regions such as Mozambique and Brazil, respectively, the prevalence of these strains is still low and this could be due to biological particularities of the circulating MtbB strains and/or differentiated host susceptibility.

Objective

To characterize genetically and phenotypically MtbB strains isolated in Brazil (n = 8) and Mozambique (n = 17).

Methods

This is a descriptive study of genotypes of the MtbB isolates, determined by spoligotyping, MIRU-VNTR typing, analysis of the IS6110 copy number in the NTF region and screening for mutations in mutT2, mutT4, rpoB, katG and pks 15/1 genes. Virulence-associated properties of the studied isolates were verified in the in vitro model of infection of human THP-1 cells.

Results

The genotypes defined by the 24VNTRs were distinct for all isolates included in this study and presented an HGDI of 0.997. The VNTR patterns with seven copies of MIRU26 and seven copies of QUB26, representative for the previously described MtbB genotype B0, dominant in Russia, were detected in 38.5% of the studied isolates. In addition, all isolates presented RD105 deletion and a 7 bp insertion in pks15/1 gene. Almost all tested strains belonged to the RD181 sublineage, with the exception of two strains from Mozambique of RD150 sublineage. Combined analysis of the NTF region integrity and mutations in mutT genes showed that 62.5% and 47% of isolates obtained in Brazil and Mozambique, respectively, were of the ancestral genotype. The virulence index of the ancient isolates, evaluated in the THP-1 cells, was significantly lower than that of the modern genotype group.

Conclusions

These data demonstrate genotype particularities of the Beijing strains isolated in Brazil and Mozambique, two countries of low prevalence of the MtbB lineage in local Mtb populations. In contrast to the neighboring countries with high prevalence of the MtbB strains of modern sublineage, significant proportions of the isolates obtained in Brazil and Mozambique were presented by the strains of the ancient sublineage. Our data suggest that lower virulence of the ancient strains, compared with the modern strains, could be involved in the slow spread of the MtbB strains in some regions.

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Keywords : Mycobacterium tuberculosis, Beijing, Mozambique and Brazil, Genotypes, Virulence


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Vol 95 - N° S1

P. S190-S196 - juin 2015 Retour au numéro
Article précédent Article précédent
  • Tuberculosis – A global emergency: Tools and methods to monitor, understand, and control the epidemic with specific example of the Beijing lineage
  • David Couvin, Nalin Rastogi
| Article suivant Article suivant
  • Novel laboratory diagnostic tests for tuberculosis and their potential role in an integrated and tiered laboratory network
  • Akos Somoskovi

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